Variant chr1-116120945-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152367.3(MAB21L3):c.62G>A(p.Arg21His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R21C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

MAB21L3
NM_152367.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

Variant links:

Genes affected

MAB21L3 (HGNC:26787): (mab-21 like 3)

MAB21L3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044710785).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAB21L3	NM_152367.3 link	c.62G>A	p.Arg21His	missense_variant	4/8	ENST00000369500.4	NP_689580.2	Q8N8X9
MAB21L3	XM_047444823.1 link	c.62G>A	p.Arg21His	missense_variant	3/7		XP_047300779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MAB21L3	ENST00000369500.4 link	c.62G>A	p.Arg21His	missense_variant	4/8	2	NM_152367.3	ENSP00000358512.3	Q8N8X9
MAB21L3	ENST00000683341.1 link	c.62G>A	p.Arg21His	missense_variant	3/7			ENSP00000508049.1	Q8N8X9
MAB21L3	ENST00000684484.1 link	c.62G>A	p.Arg21His	missense_variant	3/7			ENSP00000506754.1	Q8N8X9

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000207

AC:

AN:

251234

Hom.:

AF XY:

0.000214

AC XY:

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000719

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000158

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000166

AC:

243

AN:

1461758

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

136

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000138

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000145

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000218

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000255

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2024

The c.62G>A (p.R21H) alteration is located in exon 3 (coding exon 2) of the MAB21L3 gene. This alteration results from a G to A substitution at nucleotide position 62, causing the arginine (R) at amino acid position 21 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.071

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.71

M_CAP

Benign

0.0026

MetaRNN

Benign

0.045

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.1

REVEL

Benign

0.048

Sift

Benign

0.34

Sift4G

Benign

0.52

Polyphen

0.014

Vest4

0.15

MVP

0.39

MPC

0.071

ClinPred

0.011

GERP RS

1.9

Varity_R

0.064

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over